Nondestructive measurement technology of phenotype can provide substantial phenotypic data support for applications such as seedling breeding,management,and quality testing.The current method of measuring seedling phe...Nondestructive measurement technology of phenotype can provide substantial phenotypic data support for applications such as seedling breeding,management,and quality testing.The current method of measuring seedling phenotypes mainly relies on manual measurement which is inefficient,subjective and destroys samples.Therefore,the paper proposes a nondestructive measurement method for the canopy phenotype of the watermelon plug seedlings based on deep learning.The Azure Kinect was used to shoot canopy color images,depth images,and RGB-D images of the watermelon plug seedlings.The Mask-RCNN network was used to classify,segment,and count the canopy leaves of the watermelon plug seedlings.To reduce the error of leaf area measurement caused by mutual occlusion of leaves,the leaves were repaired by CycleGAN,and the depth images were restored by image processing.Then,the Delaunay triangulation was adopted to measure the leaf area in the leaf point cloud.The YOLOX target detection network was used to identify the growing point position of each seedling on the plug tray.Then the depth differences between the growing point and the upper surface of the plug tray were calculated to obtain plant height.The experiment results show that the nondestructive measurement algorithm proposed in this paper achieves good measurement performance for the watermelon plug seedlings from the 1 true-leaf to 3 true-leaf stages.The average relative error of measurement is 2.33%for the number of true leaves,4.59%for the number of cotyledons,8.37%for the leaf area,and 3.27%for the plant height.The experiment results demonstrate that the proposed algorithm in this paper provides an effective solution for the nondestructive measurement of the canopy phenotype of the plug seedlings.展开更多
Exosomes have shown good potential in ischemic injury disease treatments.However,evidence about their effect and molecular mechanisms in osteonecrosis of femoral head(ONFH)treatment is still limited.Here,we revealed t...Exosomes have shown good potential in ischemic injury disease treatments.However,evidence about their effect and molecular mechanisms in osteonecrosis of femoral head(ONFH)treatment is still limited.Here,we revealed the cell biology characters of ONFH osteonecrosis area bone tissue in single cell scale and thus identified a novel ONFH treatment approach based on M2 macrophages-derived exosomes(M2-Exos).We further show that M2-Exos are highly effective in the treatment of ONFH by modulating the phenotypes communication between neutrophil and endothelium including neutrophil extracellular traps formation and endothelial phenotype transition.Additionally,we identified that M2-Exos’therapeutic effect is attributed to the high content of miR-93-5p and constructed miR-93-5p overexpression model in vitro and in vivo based on lentivirus and adenoassociated virus respectively.Then we found miR-93-5p can not only reduce neutrophil extracellular traps formation but also improve angiogenic ability of endothelial cells.These results provided a new theoretical basis for the clinical application of ONFH therapeutic exosomes.展开更多
The mussel is one of the main cultivated species in the world.A significant challenge faced by suspension-cultured mussels is the high incidence of mussel fall-off from cultivation ropes,adversely impacting harvest yi...The mussel is one of the main cultivated species in the world.A significant challenge faced by suspension-cultured mussels is the high incidence of mussel fall-off from cultivation ropes,adversely impacting harvest yields,which have been documented at commercial mussel farms in the United Kingdom,the United States of America,Canada,Spain,New Zealand and China.Byssus is an important attachment structure for marine mussels,and weakness in byssal thread attachment is a major factor leading to mussel detachment from ropes.To investigate the relationship between genetic variability and byssal thread phenotypic characteristics in the hard-shelled mussel(Mytilus coruscus),we collected three wild populations of M.coruscus from different latitudes in the East China Sea,including the Shengsi(SS),Jiaojiang(JJ),and Fuding(FD)populations.The genetic diversity and structure of these populations were investigated using 10 microsatellite loci.The mean observed heterozygosity(Ho)in the SS population was 0.44,higher than the mean Ho values of the JJ(0.40)and FD(0.39)populations.The mean inbreeding coefficients(F_(is))in the SS population was 0.20,lower than the mean F_(is)values of the JJ(0.33)and FD populations(0.40).These results revealed that the SS population exhibited higher genetic diversity compared to the other two populations.The different numbers of private alleles(P_(a))in the three populations,ranging from 10 to 17,suggest that these populations have experienced selective pressures from various environments.Moreover,genetic differentiation was observed in the genetic distance between the SS population and the other two populations.We also examined the phenotypic characteristics of their byssal threads.There were significant differences in byssus attachment strength among the three populations,with the SS population located at the highest latitude secreting more byssal threads and exhibiting greater byssal breaking force and plaque adhesion strength,while the Fuding(FD)population located at the lowest latitude had the weakest byssal attachment.The observed differentiation in private alleles and byssus phenotypes might suggest that the three wild populations have experienced different environmental selective pressures.This study provides insight for future genetic enhancement programs aimed at improving byssus attachment in M.coruscus.展开更多
Hypertrophic cardiomyopathy(HCM)is the most common genetic cardiovascular disease,mostly inherited in an autosomal dominant manner.It is a global heart disease with complex clinical phenotypes and gene expression.The ...Hypertrophic cardiomyopathy(HCM)is the most common genetic cardiovascular disease,mostly inherited in an autosomal dominant manner.It is a global heart disease with complex clinical phenotypes and gene expression.The prevalence rate in the population is 1:500-1:200.This article mainly introduces the diagnostic criteria,pathological manifestations,and genetic basis of HCM,which is the leading cause of sudden death in adolescents and athletes due to exercise,with 60%-70%showing familial clustering.It also discusses the latest progress in the relationship between different genotypes and clinical phenotypes of HCM pa-tients.展开更多
The Rh blood group system,especially the D antigen,is crucial in transfusion medicine and obstetrics.Weak D phenotypes,caused by mutations in the Rhesus D antigen(RhD)blood group(RHD)gene,result in reduced antigen exp...The Rh blood group system,especially the D antigen,is crucial in transfusion medicine and obstetrics.Weak D phenotypes,caused by mutations in the Rhesus D antigen(RhD)blood group(RHD)gene,result in reduced antigen expression,posing challenges in serological testing and clinical management.Variability in detection methods leads to inconsistent results,making accurate classification difficult.Molecular techniques like polymerase chain reaction and DNA sequencing have significantly improved the identification of weak D variants,offering more reliable transfusion strategies and reducing the risk of alloimmunization.However,challenges such as lack of standardized protocols,cost constraints,and population-specific variations remain.In obstetrics,proper management of pregnant women with weak D is essential to prevent hemolytic disease of the fetus and newborn.Non-invasive prenatal testing using cell-free fetal DNA shows promise in predicting RhD incompatibility and minimizing unnecessary Rh immune globulin administration.Future advancements in highthroughput genotyping and discovery of novel RHD alleles could enhance RhD testing accuracy and efficiency.Standardizing RHD genotyping and adopting genotype-based management strategies for Rh immune globulin therapy and red blood cell transfusions will improve patient safety and clinical outcomes.This review examines the molecular basis,challenges,and future prospects in weak D phenotype management.展开更多
Thrombin blockers have been shown to be effective for various pathological conditions,but their use is limited due to the potential for serious bleeding adverse effects.This study introduced a novel bioactive peptide(...Thrombin blockers have been shown to be effective for various pathological conditions,but their use is limited due to the potential for serious bleeding adverse effects.This study introduced a novel bioactive peptide(P-2-CG) from oyster,that mitigated thrombin-mediated barrier dysfunction and prothrombotic phenotypes in human pulmonary microvascular endothelial cells(HPMECs).P-2-CG significantly attenuated the increase in endothelial monolayer permeability induced by thrombin through the possible attenuation of RhoA activation and it promoted barrier recovery by enhancing endothelial cell adhesion.Additionally,P-2-CG was found to decrease the pro-thrombotic phenotype induced by thrombin in HPMEC by reducing the extrinsic trigger tissue factor mRNA expression,which resulted in prolonged plasma clotting time,decreased Factor Xa activation,and reduced thrombin generation.Moreover,P-2-CG inhibited thrombosis efficiently by blocking intercellular adhesion molecule 1 and vascular cell adhesion protein 1 expression via tyrosine phosphorylation of nuclear factor-κB p65.P-2-CG inhibits thrombin mediated inflammation and provides a potential therapeutic option for treating endothelial dysfunction and thrombosis.展开更多
Large for gestational age(LGA)infants—defined as those with birth weight above the 97th percentile—constitute approximately 3%of all newborns.The genetic underpinnings of LGA are increasingly recognized,with associa...Large for gestational age(LGA)infants—defined as those with birth weight above the 97th percentile—constitute approximately 3%of all newborns.The genetic underpinnings of LGA are increasingly recognized,with associations reported in rare syndromes such as Pallister-Killian syndrome and Beckwith-Wiedemann syndrome.These disorders typically manifest as generalized or segmental overgrowth during the fetal and/or childhood period,frequently accompanied by tall stature,visceromegaly,and macrocephaly.展开更多
Objectives:By investigating the distinct speech and voice phenotype among TCM constitution for adults,this study aims at providing a convenient and objective methodological reference for judging TCM constitution.Metho...Objectives:By investigating the distinct speech and voice phenotype among TCM constitution for adults,this study aims at providing a convenient and objective methodological reference for judging TCM constitution.Methods:Acoustic analysis and TCM constitution assessment were performed for all 620 participants using Praat software and the CCMQ,respectively.Results:For formant features,the speech duration of special constitution participants was shorter than that of neutral,phlegm-dampness,dampness-heat,Yin-deficiency,or Yang-deficiency participants when pronuncing the vowels/a/,/i/,and/u/.Compare to Yang-deficiency,Qi-deficiency participants had a shorter speech duration when pronucing/i/.For/u/,blood-stasis participants exhibited a lower F1 value than neutral participants.For vocal features,special constitution participants showed higher local jitter than neutral,dampness-heat,and Yang-deficiency participants(for/a/,/i/,and/u/).Higher absolute local jitter than neutral or dampness-heat participants.Compared with neutral or Yang-deficiency participants,special participants owned a higher local shimmer(dB).Special participants had a lower harmonicity autocorrelation than neutral,dampness-heat,or Yang-deficiency participants.Conclusions:Formant features may effectively differentiate special constitution from neutral,phlegm-dampness,dampness-heat,Yin-deficiency,or Yang-deficiency constitutions based on vowel duration measurements(/a/,/i/,/u/).For the vowel/u/,F1 values may help distinguish blood-stasis from neutral constitution.Vocal features appear particularly useful for distinguishing special constitution from neutral,dampness-heat,or Yang-deficiency constitution,with local jitter and harmonicity autocorrelation showing significant discriminatory power.展开更多
Highlights●CRISPR/Cas9 RNP complex-based strategy demonstrates robustness and accuracy in generating gene-edited sheep.●Sheep horn development remains unaffected by partial RXFP2 knockout.●Partial RXFP2 knockout re...Highlights●CRISPR/Cas9 RNP complex-based strategy demonstrates robustness and accuracy in generating gene-edited sheep.●Sheep horn development remains unaffected by partial RXFP2 knockout.●Partial RXFP2 knockout results in unilateral cryptorchidism in sheep.展开更多
Automatic collecting of phenotypic information from plants has become a trend in breeding and smart agriculture.Targeting mature soybean plants at the harvesting stage,which are dense and overlapping,we have proposed ...Automatic collecting of phenotypic information from plants has become a trend in breeding and smart agriculture.Targeting mature soybean plants at the harvesting stage,which are dense and overlapping,we have proposed the SPP-extractor(soybean plant phenotype extractor)algorithm to acquire phenotypic traits.First,to address the mutual occultation of pods,we augmented the standard YOLOv5s model for target detection with an additional attention mechanism.The resulting model could accurately identify pods and stems and could count the entire pod set of a plant in a single scan.Second,considering that mature branches are usually bent and covered with pods,we designed a branch recognition and measurement module combining image processing,target detection,semantic segmentation,and heuristic search.Experimental results on real plants showed that SPP-extractor achieved respective R^(2) scores of 0.93–0.99 for four phenotypic traits,based on regression on manual measurements.展开更多
Differentiated adenocarcinoma of the stomach is classified into gastric or intestinal phenotypes based on mucus expression. Recent advances in mucin histochemistry and immunohistochemistry have highlighted the importa...Differentiated adenocarcinoma of the stomach is classified into gastric or intestinal phenotypes based on mucus expression. Recent advances in mucin histochemistry and immunohistochemistry have highlighted the importance of such a distinction, and it is important clinically to distinguish between gastricand intestinal-type differentiated adenocarcinoma. However, a clinical and pathological diagnosis of this type is often difficult in early gastric cancer because of histological similarities between a hyperplastic epithelium and lowgrade atypia. Furthermore, determining tumor margins is often difficult, even with extensive preoperative examination. It is therefore critical to consider these diagnostic difficulties and different biological behaviors with high malignant potential when treating patients with gastric-type differentiated adenocarcinoma.展开更多
[Objective] The aim was to conduct non-destructive monitoring on wheat leaf in field and discuss the method to measure geometric phenotype of flag leaf through digital image processing in order to establish relationsh...[Objective] The aim was to conduct non-destructive monitoring on wheat leaf in field and discuss the method to measure geometric phenotype of flag leaf through digital image processing in order to establish relationship between geometric pheno- type of flag leaf and N fertilizer regulation. [Method] Ningmai 13 was applied with N fertilizers in different amounts to discuss relationship among area, length, average width of flag leaf and applied N fertilizers using digital camera and digital image pro- cessing technique. [Result] Fertilizer is a main environmental factor influencing geo- metric phenotype of flag leaf, for example, area of flag leaf would enlarge four times and the length would increase from 15.87 to 25.33 cm by different N fertilizer amount. Thus, geometric phenotype of flag leaf would reflect N fertilizer amount at early stage. The highly accurate relationship between phenotype and N fertilizer is a reliable tech- nique to study on rules of wheat phenotype, N fertilizer and environmental factors. [Conclusion] The research indicated that digital image processing technique with scale label and dynamic background plates is an effective method to obtain geometric phenotype of sessile crops and crops with little leaf, providing a feasible scheme for non- destructive monitoring on growth dynamic of leaf＇s organs.展开更多
Aim Following cerebral isehemia, microglia respond to the injury acting as the first defense of central nervous system. Activated microglia play a dual role in the ischemie injury depending on the phenotype of micro-...Aim Following cerebral isehemia, microglia respond to the injury acting as the first defense of central nervous system. Activated microglia play a dual role in the ischemie injury depending on the phenotype of micro- gila, including deleterious M1 phenotype and neuroprotective M2 phenotype. However, microglia show transient M2 phenotype followed by a transition to M1 phenotype aggravating the ischemic injury. Many signal pathways par- ticipate in the modulation of microglial polarization , presenting potential therapeutic targets for selectively inducing the polarization of M2 microglia. In this review, we discuss M2 microglia phenotype mediated neuroprotective role and the signaling cascades controlling microglial phenotype after ischemic stroke.展开更多
Objective:Triple-negative breast cancer(estrogen receptor-negative,progesterone receptor-negative and Her2-negative) can be classified into two subtypes:basal and non-basal phenotype.And the basal phenotype is associa...Objective:Triple-negative breast cancer(estrogen receptor-negative,progesterone receptor-negative and Her2-negative) can be classified into two subtypes:basal and non-basal phenotype.And the basal phenotype is associated with poor outcome.The purpose of this study was to figure out the differences of clinicopathological characters and related factors of prognosis between these two subtypes.Methods:Immunohistochemical staining was performed for the CK5/6,CK17 basal markers and EGFR on biopsy samples from 40 triple-negative patients and the clinicopathology features of these samples were investigated.Results:Seventy percent of the patients were diagnosed as the basal phenotype.Compared with the non-basal phenotype,the basal phenotype lesions were significantly larger in diameter with a high nuclear grade.In the node-negative group the basal phenotype clearly showed the same clinicopathological differences.There was statistically significant concordance among all three antibodies.Conclusion:Expression of basal markers identifies a biologically and clinically distinct subgroup of TN tumors,justifying the use of basal markers to define the basal or the non-basal phenotype.It is important to help the doctor deciding the therapeutic strategy for patient with triple-negative breast cancer.展开更多
Discovering genetic basis of diseases is an important goal and a challenging problem in bioinformatics research. Inspired by network-based global inference approach, Semi-global inference method is proposed to capture...Discovering genetic basis of diseases is an important goal and a challenging problem in bioinformatics research. Inspired by network-based global inference approach, Semi-global inference method is proposed to capture the complex associations between phenotypes and genes. The proposed method integrates phenotype similarities and protein-protein interactions, and it establishes the profile vectors of phenotypes and proteins. Then the relevance between each candidate gene and the target phenotype is evaluated. Candidate genes are then ranked according to relevance mark and genes that are potentially associated with target disease are identified based on this ranking. The model selects nodes in integrated phenotype-protein network for inference, by exploiting Phenotype Similarity Threshold (PST), which throws lights on selection of similar phenotypes for gene prediction problem. Different vector relevance metrics for computing the relevance marks of candidate genes are discussed. The performance of the model is evaluated on Online Mendelian Inheritance in Man (OMIM) data sets and experimental evaluation shows high performance of proposed Semi-global method outperforms existing global inference methods.展开更多
[Objective]The aim was to investigate inheritance of the mutagenic properties caused by ion implantation from F1 to F2 generation in chili pepper.[Method]Chili pepper seeds were implanted with different ion combinatio...[Objective]The aim was to investigate inheritance of the mutagenic properties caused by ion implantation from F1 to F2 generation in chili pepper.[Method]Chili pepper seeds were implanted with different ion combinations at different doses,and the F1 generation seeds of five groups in which biological mutation occurred were selected to sow in the field.Then the main phenotype changes in F2 generation were observed,the biochemical changes caused by ion implantation were analyzed by determination of peroxidase isozyme.[Result]Seed implanted with 9×1011 P2＋/cm2 and 1×1012 Cu2＋/cm2（No.21）on its both sides could maintain the superiority in yield per plant to F2 generation,while the mutagenic effects of F1 generation in other groups were not inherited by the F2 generation.[Conclusion]The prominent biological characters induced in the seeds of group No.21 were relatively inherited,so the seeds were worth further breeding.展开更多
AIM:To investigate the in vitro antitumor effect of adenovirus-mediated small interfering RNAs(siRNAs)on pancreatic cancer and the associated mechanism.METHODS:A 63-nucleotide(nt)oligonucleotide encoding K-rasval12 an...AIM:To investigate the in vitro antitumor effect of adenovirus-mediated small interfering RNAs(siRNAs)on pancreatic cancer and the associated mechanism.METHODS:A 63-nucleotide(nt)oligonucleotide encoding K-rasval12 and specific siRNA were introduced into pSilencer 3.1-H1,then the H1-RNA promoter and siRNA coding insert were subcloned into pAdTrack to get plasmid pAdTrackH1-Avasval12.After homologous recombination in bacteria and transfections of such plasmids into a mammalian packaging cell line 293,siRNA expressing adenovirus Adh1-K-rasval12 was obtained.Stable suppression of K-rasval12 was detected by Northern blot and Western blot.Apoptosis in Panc-1 cells was detected by flow cytometry.RESULTS:We obtained adenovirus AdHl-K-rasval12 carrying the pSilencer 3.1-H1 cassette,which could mediate gene silencing.Through siRNA targeted K-rasval12,the oncogenic phenotype of cancer cells was reversed.Flow cytometry showed that apoptotic index of Panc-1 cells was significantly higher in the AdH1-K-rasval12-treatment group(18.70%at 72 h post-infection,49.55%at 96 h post-infection)compared to the control groups(3.47%,3.98%at 72 and 96 h post-infection of AdH1-empty,respectively;4.21%,3.78%at 72 and 96 h post-infection of AdHl-p53,respectively)(P<0.05).CONCLUSION:These results demonstrate that adenoviral vectors can be used to mediate RNA interference(RNAi)to induce persistent loss of functional phenotypes.In gene therapy,the selective down-regulation of only the mutant version of a gene allows for highly specific effects on tumor cells,while leaving the normal cells untouched.In addition,the apoptosis of pancreatic cancer cell line Panc-1 can be induced after AdH1-K-rasval12 infection.This kind of adenovirus based on RNAi might be a promising vector for cancer therapy.展开更多
Adipose tissue is a rich, ubiquitous and easily acces-sible source for multipotent stromal/stem cells and has, therefore, several advantages compared to other sourc-es of mesenchymal stromal/stem cells. Several studie...Adipose tissue is a rich, ubiquitous and easily acces-sible source for multipotent stromal/stem cells and has, therefore, several advantages compared to other sourc-es of mesenchymal stromal/stem cells. Several studies have tried to identify the origin of the stromal/stem cell population within adipose tissue in situ. This is a complicated attempt because no marker has currently been described which unambiguously identifies native adipose-derived stromal/stem cells(ASCs). Isolated and cultured ASCs are a non-uniform preparation consisting of several subsets of stem and precursor cells. Cultured ASCs are characterized by their expression of a panel of markers(and the absence of others), whereas their in vitro phenotype is dynamic. Some markers were ex-pressed de novo during culture, the expression of some markers is lost. For a long time, CD34 expression was solely used to characterize haematopoietic stem and progenitor cells, but now it has become evident that it is also a potential marker to identify an ASC subpopula-tion in situ and after a short culture time. Nevertheless, long-term cultured ASCs do not express CD34, perhaps due to the artificial environment. This review gives an update of the recently published data on the origin and phenotype of ASCs both in vivo and in vitro. In addition, the composition of ASCs(or their subpopula-tions) seems to vary between different laboratories andpreparations. This heterogeneity of ASC preparationsmay result from different reasons. One of the main problems in comparing results from different laborato-ries is the lack of a standardized isolation and culture protocol for ASCs. Since many aspects of ASCs, suchas the differential potential or the current use in clinical trials, are fully described in other recent reviews, this review further updates the more basic research issues concerning ASCs' subpopulations, heterogeneity andculture standardization.展开更多
AIM:IBD is a systemic disease associated with a large number of extraintestinal manifestations (EIMs).Our aim was to determine the prevalence of EIMs in a large IBD cohort in Veszprem Province in a 25-year follow-up s...AIM:IBD is a systemic disease associated with a large number of extraintestinal manifestations (EIMs).Our aim was to determine the prevalence of EIMs in a large IBD cohort in Veszprem Province in a 25-year follow-up study. METHODS:Eight hundred and seventy-three IBD patients were enrolled (ulcerative colitis/UC/:619,m/f:317/302, mean age at presentation:38.3 years,average disease duration:11.2 years;Crohn's disease/CD/:254,m/f:125/129, mean age at presentation:32.5 years,average disease duration:9.2 years).Intestinal,extraintestinal signs and laboratory tests were monitored regularly.Any alteration suggesting an EIMs was investigated by a specialist. RESULTS:A total of 21.3% of patients with IBD had EIM (UC:15.0%,CD:36.6%).Age at presentation did not affect the likelihood of EIM.Prevalence of EIMs was higher in women and in CD,ocular complications and primary sclerosing cholangitis (PSC) were more frequent in UC.In UC there was an increased tendency of EIM in patients with a more extensive disease.Joint complications were more frequent in CD (22.4% vsUC 10.2%,P<0.01).In UC positive family history increased the risk of joint complications (OR:3.63).In CD the frequency of type-1 peripheral arthritis was increased in patients with penetrating disease (P=0.028).PSC was present in 1.6% in UC and 0.8% in CD.Dermatological complications were present in 3.8% in UC and 10.2% in CD,the rate of ocular complications was around 3% in both diseases.Rare complications were glomerulonephritis,autoimmune hemolytic anaemia and celiac disease. CONCLUSION:Prevalence of EIM in Hungarian IBD patients is in concordance with data from Western countries.The high number of EIM supports a role for complex follow-up in these patients.展开更多
AIM: To determine common NOD2/CARD15 mutations and TLR4 D299G polymorphism in Hungarian patients with CD. METHODS: A total of 527 unrelated patients with CD (male/female: 265/262, age: 37.1 (SD 7.6) years) and 200 hea...AIM: To determine common NOD2/CARD15 mutations and TLR4 D299G polymorphism in Hungarian patients with CD. METHODS: A total of 527 unrelated patients with CD (male/female: 265/262, age: 37.1 (SD 7.6) years) and 200 healthy subjects were included. DNA was screened for possible NOD2/CARD15 mutations by denaturing high-performance liquid chromatography (confirmed by direct sequencing). TLR4 D299G was tested by PCR-RFLP. RESULTS: NOD2/CARD15 mutations were found in 185 patients (35.1%) and in 33 controls (16.5%,P<0.0001). SNP8/R702W (10.8% vs 6%, P= 0.02), SNP13/3020insC (19.4% vs 5%, P<0.0001) and exon4 R703C (2.1% vs 0%, P= 0.02) mutations were more frequent in CD, while the frequency of SNP12/G908R was not increased. The frequency of TLR4 D299G was not different (CD: 9.9% vs controls: 12.0%). Variant NOD2/CARD15 allele was associated with an increased risk for CD (ORhet=1.71, 95%CI=1.12-2.6, P= 0.0001, ORtwo-risk alleles = 25.2, 95%CI =4.37- ,P<0.0001), early disease onset (carrier: 26.4 years vs non-carrier: 29.8 years, P=0.0006), ileal disease (81.9% (?) 69.5%, OR = 1.99, 95%CI = 1.29-3.08, P= 0.02, presence of NOD2/CARD15 and TLR4: 86.7% vs 64.8%), stricturing behavior (OR = 1.69,95%CI = 1.13-2.55, P= 0.026) and increased need for resection (OR=1.71, 95%CI: 1.13-2.62, P= 0.01), but not with duration, extra-intestinal manifestations, familial disease or smoking. TLR4 exhibited a modifier effect: age of onset in wt/TLR4 D299G carriers: 27.4 years vs NOD2mut/TLR D299G: 23 years (P = 0.06), in NOD2mut/wt: 26.7 years. CONCLUSION: These results confirm that variant NOD2/ CARD15 (R702W, R703C and 3020insC) alleles are associated with earlier disease onset, ileal disease, stricturing disease behavior in Hungarian CD patients. In contrast, although the frequency of TLR4 D299G polymorphism was not different from controls, NOD2/TLR4 mutation carriers tended to present at earlier age.展开更多
基金funded by the National Key Research and Development Program of China(Grant No.2019YFD1001900)the HZAU-AGIS Cooperation Fund(Grant No.SZYJY2022006).
文摘Nondestructive measurement technology of phenotype can provide substantial phenotypic data support for applications such as seedling breeding,management,and quality testing.The current method of measuring seedling phenotypes mainly relies on manual measurement which is inefficient,subjective and destroys samples.Therefore,the paper proposes a nondestructive measurement method for the canopy phenotype of the watermelon plug seedlings based on deep learning.The Azure Kinect was used to shoot canopy color images,depth images,and RGB-D images of the watermelon plug seedlings.The Mask-RCNN network was used to classify,segment,and count the canopy leaves of the watermelon plug seedlings.To reduce the error of leaf area measurement caused by mutual occlusion of leaves,the leaves were repaired by CycleGAN,and the depth images were restored by image processing.Then,the Delaunay triangulation was adopted to measure the leaf area in the leaf point cloud.The YOLOX target detection network was used to identify the growing point position of each seedling on the plug tray.Then the depth differences between the growing point and the upper surface of the plug tray were calculated to obtain plant height.The experiment results show that the nondestructive measurement algorithm proposed in this paper achieves good measurement performance for the watermelon plug seedlings from the 1 true-leaf to 3 true-leaf stages.The average relative error of measurement is 2.33%for the number of true leaves,4.59%for the number of cotyledons,8.37%for the leaf area,and 3.27%for the plant height.The experiment results demonstrate that the proposed algorithm in this paper provides an effective solution for the nondestructive measurement of the canopy phenotype of the plug seedlings.
基金the support of the National Natural Science Foundation of China (Grant No.82272503)Natural Science Foundation of Zhejiang Province (Grant No. LQN25H060006)
文摘Exosomes have shown good potential in ischemic injury disease treatments.However,evidence about their effect and molecular mechanisms in osteonecrosis of femoral head(ONFH)treatment is still limited.Here,we revealed the cell biology characters of ONFH osteonecrosis area bone tissue in single cell scale and thus identified a novel ONFH treatment approach based on M2 macrophages-derived exosomes(M2-Exos).We further show that M2-Exos are highly effective in the treatment of ONFH by modulating the phenotypes communication between neutrophil and endothelium including neutrophil extracellular traps formation and endothelial phenotype transition.Additionally,we identified that M2-Exos’therapeutic effect is attributed to the high content of miR-93-5p and constructed miR-93-5p overexpression model in vitro and in vivo based on lentivirus and adenoassociated virus respectively.Then we found miR-93-5p can not only reduce neutrophil extracellular traps formation but also improve angiogenic ability of endothelial cells.These results provided a new theoretical basis for the clinical application of ONFH therapeutic exosomes.
文摘The mussel is one of the main cultivated species in the world.A significant challenge faced by suspension-cultured mussels is the high incidence of mussel fall-off from cultivation ropes,adversely impacting harvest yields,which have been documented at commercial mussel farms in the United Kingdom,the United States of America,Canada,Spain,New Zealand and China.Byssus is an important attachment structure for marine mussels,and weakness in byssal thread attachment is a major factor leading to mussel detachment from ropes.To investigate the relationship between genetic variability and byssal thread phenotypic characteristics in the hard-shelled mussel(Mytilus coruscus),we collected three wild populations of M.coruscus from different latitudes in the East China Sea,including the Shengsi(SS),Jiaojiang(JJ),and Fuding(FD)populations.The genetic diversity and structure of these populations were investigated using 10 microsatellite loci.The mean observed heterozygosity(Ho)in the SS population was 0.44,higher than the mean Ho values of the JJ(0.40)and FD(0.39)populations.The mean inbreeding coefficients(F_(is))in the SS population was 0.20,lower than the mean F_(is)values of the JJ(0.33)and FD populations(0.40).These results revealed that the SS population exhibited higher genetic diversity compared to the other two populations.The different numbers of private alleles(P_(a))in the three populations,ranging from 10 to 17,suggest that these populations have experienced selective pressures from various environments.Moreover,genetic differentiation was observed in the genetic distance between the SS population and the other two populations.We also examined the phenotypic characteristics of their byssal threads.There were significant differences in byssus attachment strength among the three populations,with the SS population located at the highest latitude secreting more byssal threads and exhibiting greater byssal breaking force and plaque adhesion strength,while the Fuding(FD)population located at the lowest latitude had the weakest byssal attachment.The observed differentiation in private alleles and byssus phenotypes might suggest that the three wild populations have experienced different environmental selective pressures.This study provides insight for future genetic enhancement programs aimed at improving byssus attachment in M.coruscus.
基金Supported by National Natural Science Foundation of China,No.82230065,No.82371974 and No.82272009.
文摘Hypertrophic cardiomyopathy(HCM)is the most common genetic cardiovascular disease,mostly inherited in an autosomal dominant manner.It is a global heart disease with complex clinical phenotypes and gene expression.The prevalence rate in the population is 1:500-1:200.This article mainly introduces the diagnostic criteria,pathological manifestations,and genetic basis of HCM,which is the leading cause of sudden death in adolescents and athletes due to exercise,with 60%-70%showing familial clustering.It also discusses the latest progress in the relationship between different genotypes and clinical phenotypes of HCM pa-tients.
文摘The Rh blood group system,especially the D antigen,is crucial in transfusion medicine and obstetrics.Weak D phenotypes,caused by mutations in the Rhesus D antigen(RhD)blood group(RHD)gene,result in reduced antigen expression,posing challenges in serological testing and clinical management.Variability in detection methods leads to inconsistent results,making accurate classification difficult.Molecular techniques like polymerase chain reaction and DNA sequencing have significantly improved the identification of weak D variants,offering more reliable transfusion strategies and reducing the risk of alloimmunization.However,challenges such as lack of standardized protocols,cost constraints,and population-specific variations remain.In obstetrics,proper management of pregnant women with weak D is essential to prevent hemolytic disease of the fetus and newborn.Non-invasive prenatal testing using cell-free fetal DNA shows promise in predicting RhD incompatibility and minimizing unnecessary Rh immune globulin administration.Future advancements in highthroughput genotyping and discovery of novel RHD alleles could enhance RhD testing accuracy and efficiency.Standardizing RHD genotyping and adopting genotype-based management strategies for Rh immune globulin therapy and red blood cell transfusions will improve patient safety and clinical outcomes.This review examines the molecular basis,challenges,and future prospects in weak D phenotype management.
基金supported by The National Natural Science Foundation of China (32130085 and 32202021)。
文摘Thrombin blockers have been shown to be effective for various pathological conditions,but their use is limited due to the potential for serious bleeding adverse effects.This study introduced a novel bioactive peptide(P-2-CG) from oyster,that mitigated thrombin-mediated barrier dysfunction and prothrombotic phenotypes in human pulmonary microvascular endothelial cells(HPMECs).P-2-CG significantly attenuated the increase in endothelial monolayer permeability induced by thrombin through the possible attenuation of RhoA activation and it promoted barrier recovery by enhancing endothelial cell adhesion.Additionally,P-2-CG was found to decrease the pro-thrombotic phenotype induced by thrombin in HPMEC by reducing the extrinsic trigger tissue factor mRNA expression,which resulted in prolonged plasma clotting time,decreased Factor Xa activation,and reduced thrombin generation.Moreover,P-2-CG inhibited thrombosis efficiently by blocking intercellular adhesion molecule 1 and vascular cell adhesion protein 1 expression via tyrosine phosphorylation of nuclear factor-κB p65.P-2-CG inhibits thrombin mediated inflammation and provides a potential therapeutic option for treating endothelial dysfunction and thrombosis.
文摘Large for gestational age(LGA)infants—defined as those with birth weight above the 97th percentile—constitute approximately 3%of all newborns.The genetic underpinnings of LGA are increasingly recognized,with associations reported in rare syndromes such as Pallister-Killian syndrome and Beckwith-Wiedemann syndrome.These disorders typically manifest as generalized or segmental overgrowth during the fetal and/or childhood period,frequently accompanied by tall stature,visceromegaly,and macrocephaly.
基金supported by the National Natural Science Foundation of China(Nos.81730107 and 81973883)the National Science&Technology Basic Research Project(No.2015FY111700)the Shanghai Pudong New District New Area Project(No.PW2022A-78(WQZ)).
文摘Objectives:By investigating the distinct speech and voice phenotype among TCM constitution for adults,this study aims at providing a convenient and objective methodological reference for judging TCM constitution.Methods:Acoustic analysis and TCM constitution assessment were performed for all 620 participants using Praat software and the CCMQ,respectively.Results:For formant features,the speech duration of special constitution participants was shorter than that of neutral,phlegm-dampness,dampness-heat,Yin-deficiency,or Yang-deficiency participants when pronuncing the vowels/a/,/i/,and/u/.Compare to Yang-deficiency,Qi-deficiency participants had a shorter speech duration when pronucing/i/.For/u/,blood-stasis participants exhibited a lower F1 value than neutral participants.For vocal features,special constitution participants showed higher local jitter than neutral,dampness-heat,and Yang-deficiency participants(for/a/,/i/,and/u/).Higher absolute local jitter than neutral or dampness-heat participants.Compared with neutral or Yang-deficiency participants,special participants owned a higher local shimmer(dB).Special participants had a lower harmonicity autocorrelation than neutral,dampness-heat,or Yang-deficiency participants.Conclusions:Formant features may effectively differentiate special constitution from neutral,phlegm-dampness,dampness-heat,Yin-deficiency,or Yang-deficiency constitutions based on vowel duration measurements(/a/,/i/,/u/).For the vowel/u/,F1 values may help distinguish blood-stasis from neutral constitution.Vocal features appear particularly useful for distinguishing special constitution from neutral,dampness-heat,or Yang-deficiency constitution,with local jitter and harmonicity autocorrelation showing significant discriminatory power.
基金supported by the National Key Research and Development Program of China(2022YFD1300200)the National Natural Science Foundation of China(32161143010,32202646,and 32272848)+2 种基金the China Agriculture Research System(CARS-39)the Key Special Project of Ningxia Science and Technology Department,China(2021BEF02024)the local grants,China(NXTS2021-001,2022GD-TSLD-46,NK2022010207,and NXTS2022-001)。
文摘Highlights●CRISPR/Cas9 RNP complex-based strategy demonstrates robustness and accuracy in generating gene-edited sheep.●Sheep horn development remains unaffected by partial RXFP2 knockout.●Partial RXFP2 knockout results in unilateral cryptorchidism in sheep.
基金supported by the National Natural Science Foundation of China(62276032,32072016)the Agricultural Science and Technology Innovation Program(ASTIP)of Chinese Academy of Agricultural Sciences。
文摘Automatic collecting of phenotypic information from plants has become a trend in breeding and smart agriculture.Targeting mature soybean plants at the harvesting stage,which are dense and overlapping,we have proposed the SPP-extractor(soybean plant phenotype extractor)algorithm to acquire phenotypic traits.First,to address the mutual occultation of pods,we augmented the standard YOLOv5s model for target detection with an additional attention mechanism.The resulting model could accurately identify pods and stems and could count the entire pod set of a plant in a single scan.Second,considering that mature branches are usually bent and covered with pods,we designed a branch recognition and measurement module combining image processing,target detection,semantic segmentation,and heuristic search.Experimental results on real plants showed that SPP-extractor achieved respective R^(2) scores of 0.93–0.99 for four phenotypic traits,based on regression on manual measurements.
文摘Differentiated adenocarcinoma of the stomach is classified into gastric or intestinal phenotypes based on mucus expression. Recent advances in mucin histochemistry and immunohistochemistry have highlighted the importance of such a distinction, and it is important clinically to distinguish between gastricand intestinal-type differentiated adenocarcinoma. However, a clinical and pathological diagnosis of this type is often difficult in early gastric cancer because of histological similarities between a hyperplastic epithelium and lowgrade atypia. Furthermore, determining tumor margins is often difficult, even with extensive preoperative examination. It is therefore critical to consider these diagnostic difficulties and different biological behaviors with high malignant potential when treating patients with gastric-type differentiated adenocarcinoma.
基金Supported by National Natural Science Foundation of China (50875131)~~
文摘[Objective] The aim was to conduct non-destructive monitoring on wheat leaf in field and discuss the method to measure geometric phenotype of flag leaf through digital image processing in order to establish relationship between geometric pheno- type of flag leaf and N fertilizer regulation. [Method] Ningmai 13 was applied with N fertilizers in different amounts to discuss relationship among area, length, average width of flag leaf and applied N fertilizers using digital camera and digital image pro- cessing technique. [Result] Fertilizer is a main environmental factor influencing geo- metric phenotype of flag leaf, for example, area of flag leaf would enlarge four times and the length would increase from 15.87 to 25.33 cm by different N fertilizer amount. Thus, geometric phenotype of flag leaf would reflect N fertilizer amount at early stage. The highly accurate relationship between phenotype and N fertilizer is a reliable tech- nique to study on rules of wheat phenotype, N fertilizer and environmental factors. [Conclusion] The research indicated that digital image processing technique with scale label and dynamic background plates is an effective method to obtain geometric phenotype of sessile crops and crops with little leaf, providing a feasible scheme for non- destructive monitoring on growth dynamic of leaf＇s organs.
文摘Aim Following cerebral isehemia, microglia respond to the injury acting as the first defense of central nervous system. Activated microglia play a dual role in the ischemie injury depending on the phenotype of micro- gila, including deleterious M1 phenotype and neuroprotective M2 phenotype. However, microglia show transient M2 phenotype followed by a transition to M1 phenotype aggravating the ischemic injury. Many signal pathways par- ticipate in the modulation of microglial polarization , presenting potential therapeutic targets for selectively inducing the polarization of M2 microglia. In this review, we discuss M2 microglia phenotype mediated neuroprotective role and the signaling cascades controlling microglial phenotype after ischemic stroke.
基金Supported by a grant from the National Natural Science Foundation of Hubei Province (No.2009CDB063)
文摘Objective:Triple-negative breast cancer(estrogen receptor-negative,progesterone receptor-negative and Her2-negative) can be classified into two subtypes:basal and non-basal phenotype.And the basal phenotype is associated with poor outcome.The purpose of this study was to figure out the differences of clinicopathological characters and related factors of prognosis between these two subtypes.Methods:Immunohistochemical staining was performed for the CK5/6,CK17 basal markers and EGFR on biopsy samples from 40 triple-negative patients and the clinicopathology features of these samples were investigated.Results:Seventy percent of the patients were diagnosed as the basal phenotype.Compared with the non-basal phenotype,the basal phenotype lesions were significantly larger in diameter with a high nuclear grade.In the node-negative group the basal phenotype clearly showed the same clinicopathological differences.There was statistically significant concordance among all three antibodies.Conclusion:Expression of basal markers identifies a biologically and clinically distinct subgroup of TN tumors,justifying the use of basal markers to define the basal or the non-basal phenotype.It is important to help the doctor deciding the therapeutic strategy for patient with triple-negative breast cancer.
文摘Discovering genetic basis of diseases is an important goal and a challenging problem in bioinformatics research. Inspired by network-based global inference approach, Semi-global inference method is proposed to capture the complex associations between phenotypes and genes. The proposed method integrates phenotype similarities and protein-protein interactions, and it establishes the profile vectors of phenotypes and proteins. Then the relevance between each candidate gene and the target phenotype is evaluated. Candidate genes are then ranked according to relevance mark and genes that are potentially associated with target disease are identified based on this ranking. The model selects nodes in integrated phenotype-protein network for inference, by exploiting Phenotype Similarity Threshold (PST), which throws lights on selection of similar phenotypes for gene prediction problem. Different vector relevance metrics for computing the relevance marks of candidate genes are discussed. The performance of the model is evaluated on Online Mendelian Inheritance in Man (OMIM) data sets and experimental evaluation shows high performance of proposed Semi-global method outperforms existing global inference methods.
基金Supported by"Study on Biological Effects of Mutagenesis of Seedsof Oil Crops,Purple Peanut and Sunflower(including Chili Pepper)Caused by Ion Implantation"supported by the Key Lab for Beam Technology and Material Modification of Ministry of Education(0912)~~
文摘[Objective]The aim was to investigate inheritance of the mutagenic properties caused by ion implantation from F1 to F2 generation in chili pepper.[Method]Chili pepper seeds were implanted with different ion combinations at different doses,and the F1 generation seeds of five groups in which biological mutation occurred were selected to sow in the field.Then the main phenotype changes in F2 generation were observed,the biochemical changes caused by ion implantation were analyzed by determination of peroxidase isozyme.[Result]Seed implanted with 9×1011 P2＋/cm2 and 1×1012 Cu2＋/cm2（No.21）on its both sides could maintain the superiority in yield per plant to F2 generation,while the mutagenic effects of F1 generation in other groups were not inherited by the F2 generation.[Conclusion]The prominent biological characters induced in the seeds of group No.21 were relatively inherited,so the seeds were worth further breeding.
基金Supported by National Natural Science Foundation of China,No.30271473
文摘AIM:To investigate the in vitro antitumor effect of adenovirus-mediated small interfering RNAs(siRNAs)on pancreatic cancer and the associated mechanism.METHODS:A 63-nucleotide(nt)oligonucleotide encoding K-rasval12 and specific siRNA were introduced into pSilencer 3.1-H1,then the H1-RNA promoter and siRNA coding insert were subcloned into pAdTrack to get plasmid pAdTrackH1-Avasval12.After homologous recombination in bacteria and transfections of such plasmids into a mammalian packaging cell line 293,siRNA expressing adenovirus Adh1-K-rasval12 was obtained.Stable suppression of K-rasval12 was detected by Northern blot and Western blot.Apoptosis in Panc-1 cells was detected by flow cytometry.RESULTS:We obtained adenovirus AdHl-K-rasval12 carrying the pSilencer 3.1-H1 cassette,which could mediate gene silencing.Through siRNA targeted K-rasval12,the oncogenic phenotype of cancer cells was reversed.Flow cytometry showed that apoptotic index of Panc-1 cells was significantly higher in the AdH1-K-rasval12-treatment group(18.70%at 72 h post-infection,49.55%at 96 h post-infection)compared to the control groups(3.47%,3.98%at 72 and 96 h post-infection of AdH1-empty,respectively;4.21%,3.78%at 72 and 96 h post-infection of AdHl-p53,respectively)(P<0.05).CONCLUSION:These results demonstrate that adenoviral vectors can be used to mediate RNA interference(RNAi)to induce persistent loss of functional phenotypes.In gene therapy,the selective down-regulation of only the mutant version of a gene allows for highly specific effects on tumor cells,while leaving the normal cells untouched.In addition,the apoptosis of pancreatic cancer cell line Panc-1 can be induced after AdH1-K-rasval12 infection.This kind of adenovirus based on RNAi might be a promising vector for cancer therapy.
文摘Adipose tissue is a rich, ubiquitous and easily acces-sible source for multipotent stromal/stem cells and has, therefore, several advantages compared to other sourc-es of mesenchymal stromal/stem cells. Several studies have tried to identify the origin of the stromal/stem cell population within adipose tissue in situ. This is a complicated attempt because no marker has currently been described which unambiguously identifies native adipose-derived stromal/stem cells(ASCs). Isolated and cultured ASCs are a non-uniform preparation consisting of several subsets of stem and precursor cells. Cultured ASCs are characterized by their expression of a panel of markers(and the absence of others), whereas their in vitro phenotype is dynamic. Some markers were ex-pressed de novo during culture, the expression of some markers is lost. For a long time, CD34 expression was solely used to characterize haematopoietic stem and progenitor cells, but now it has become evident that it is also a potential marker to identify an ASC subpopula-tion in situ and after a short culture time. Nevertheless, long-term cultured ASCs do not express CD34, perhaps due to the artificial environment. This review gives an update of the recently published data on the origin and phenotype of ASCs both in vivo and in vitro. In addition, the composition of ASCs(or their subpopula-tions) seems to vary between different laboratories andpreparations. This heterogeneity of ASC preparationsmay result from different reasons. One of the main problems in comparing results from different laborato-ries is the lack of a standardized isolation and culture protocol for ASCs. Since many aspects of ASCs, suchas the differential potential or the current use in clinical trials, are fully described in other recent reviews, this review further updates the more basic research issues concerning ASCs' subpopulations, heterogeneity andculture standardization.
文摘AIM:IBD is a systemic disease associated with a large number of extraintestinal manifestations (EIMs).Our aim was to determine the prevalence of EIMs in a large IBD cohort in Veszprem Province in a 25-year follow-up study. METHODS:Eight hundred and seventy-three IBD patients were enrolled (ulcerative colitis/UC/:619,m/f:317/302, mean age at presentation:38.3 years,average disease duration:11.2 years;Crohn's disease/CD/:254,m/f:125/129, mean age at presentation:32.5 years,average disease duration:9.2 years).Intestinal,extraintestinal signs and laboratory tests were monitored regularly.Any alteration suggesting an EIMs was investigated by a specialist. RESULTS:A total of 21.3% of patients with IBD had EIM (UC:15.0%,CD:36.6%).Age at presentation did not affect the likelihood of EIM.Prevalence of EIMs was higher in women and in CD,ocular complications and primary sclerosing cholangitis (PSC) were more frequent in UC.In UC there was an increased tendency of EIM in patients with a more extensive disease.Joint complications were more frequent in CD (22.4% vsUC 10.2%,P<0.01).In UC positive family history increased the risk of joint complications (OR:3.63).In CD the frequency of type-1 peripheral arthritis was increased in patients with penetrating disease (P=0.028).PSC was present in 1.6% in UC and 0.8% in CD.Dermatological complications were present in 3.8% in UC and 10.2% in CD,the rate of ocular complications was around 3% in both diseases.Rare complications were glomerulonephritis,autoimmune hemolytic anaemia and celiac disease. CONCLUSION:Prevalence of EIM in Hungarian IBD patients is in concordance with data from Western countries.The high number of EIM supports a role for complex follow-up in these patients.
文摘AIM: To determine common NOD2/CARD15 mutations and TLR4 D299G polymorphism in Hungarian patients with CD. METHODS: A total of 527 unrelated patients with CD (male/female: 265/262, age: 37.1 (SD 7.6) years) and 200 healthy subjects were included. DNA was screened for possible NOD2/CARD15 mutations by denaturing high-performance liquid chromatography (confirmed by direct sequencing). TLR4 D299G was tested by PCR-RFLP. RESULTS: NOD2/CARD15 mutations were found in 185 patients (35.1%) and in 33 controls (16.5%,P<0.0001). SNP8/R702W (10.8% vs 6%, P= 0.02), SNP13/3020insC (19.4% vs 5%, P<0.0001) and exon4 R703C (2.1% vs 0%, P= 0.02) mutations were more frequent in CD, while the frequency of SNP12/G908R was not increased. The frequency of TLR4 D299G was not different (CD: 9.9% vs controls: 12.0%). Variant NOD2/CARD15 allele was associated with an increased risk for CD (ORhet=1.71, 95%CI=1.12-2.6, P= 0.0001, ORtwo-risk alleles = 25.2, 95%CI =4.37- ,P<0.0001), early disease onset (carrier: 26.4 years vs non-carrier: 29.8 years, P=0.0006), ileal disease (81.9% (?) 69.5%, OR = 1.99, 95%CI = 1.29-3.08, P= 0.02, presence of NOD2/CARD15 and TLR4: 86.7% vs 64.8%), stricturing behavior (OR = 1.69,95%CI = 1.13-2.55, P= 0.026) and increased need for resection (OR=1.71, 95%CI: 1.13-2.62, P= 0.01), but not with duration, extra-intestinal manifestations, familial disease or smoking. TLR4 exhibited a modifier effect: age of onset in wt/TLR4 D299G carriers: 27.4 years vs NOD2mut/TLR D299G: 23 years (P = 0.06), in NOD2mut/wt: 26.7 years. CONCLUSION: These results confirm that variant NOD2/ CARD15 (R702W, R703C and 3020insC) alleles are associated with earlier disease onset, ileal disease, stricturing disease behavior in Hungarian CD patients. In contrast, although the frequency of TLR4 D299G polymorphism was not different from controls, NOD2/TLR4 mutation carriers tended to present at earlier age.
